Through an integrated program of clinical and pharmacological research, this project continues to explore aspects of the biochemical pathophysiology of the affective disorders as well as neuropharmacological actions of the drugs used in their treatment. The longterm objectives of this research include the development of biochemical as well as clinical criteria for classifying the depressive disorders and for predicting differential clinical antidepressant responses to various forms of treatment. This research will include: studies of biochemical differences (including measures of biogenic amine metabolism) in clinically defined subtypes of depressive disorders; studies of clinical differences in groupings of depressed patients defined by various biochemical criteria; studies of the relationships among various biochemical and clinical variables in patients with depressive disorders; studies of pretreatment biochemical and clinical variables as predictors of response to antidepressant pharmacotherapy; studies of the changes in biogenic amine metabolism associated with longterm antidepressant drug administration in animals as well as man; studies of the changes in biogenic amine metabolism associated with changes in clinical state in manic and depressed patients. BIBLIOGRAPHIC REFERENCES: Roffman, M., Reigle, T.G., Orsulak, P. and Schildkraut, J.J. Properties of Catechol-O-Methyl Transferase in Soluble and Particulate Preparations from Rat Red Blood Cells. Biochem. Pharmacol. 25: 208-209, 1976. Schildkraut, J.J., Herzog, J.M., Orsulak, P.J., Edelman, S.E., Shein, H.M. and Frazier, S.H. Reduced Platelet Monoamine Oxidase Activity in a Subgroup of Schizophrenic Patients. Am. J. Psychiat. 133: 438-440, 1976.